The Chediak-Higashi Syndrome (CHS) is a systemic disease of man and animals characterized by increased size of lysosomes and subcellular granules. Although the etiology is unknown, defective microtubule assembly or function, decreased cyclic GMP and increased cyclic AMP, absent granular enzymes, altered cholinergic responsiveness, and abnormal composition of cell membranes have been proposed as causes without conclusive evidence. Preliminary work demonstrates that the CHS trait is morphologically expressed in skin fibroblasts from a human CHS patient and the beige mouse. Enlarged lysosomes are found only near the nucleus, not in a normal uniform distribution throughout the cytoplasm. Using human and beige mouse fibroblasts as a tissue source a markedly increased incorporation of 32PO4 into an unusual alkali-stable phospholipid (not sphingomyelin) has been demonstrated. 32PO4 incorporation into major phospholipid classes was not altered. The objective of this proposed research is to test the hypothesis that CHS is an inborn error of phospholipid metabolism. The unknown phospholipid will be identified and the mechanism of its accumulation ascertained. The mass of the material will be measured in whole cell lipids as well as in lysosome-enriched cell fractions. The effect of carbachol, reported to ameliorate the morphologic abnormalities of CHS lysosomes will be tested for a parallel effect on the phospholipid marker.